Preparation having enhanced sexual hormone action and process of making same



Patented Sept. 19, 1939 UNITED STATES PATENT OFFICE HORMONE MAKING SAME Karl Miescher, Riehen,

Basel, Switzerland,

Switzerland No Drawing.

ACTION AND PROCESS OF and Albert Wettstein,

assignors to the firm of S0- ciety of Chemical Industry in Basle, Basel,

Application February 10, 1937, Se-

rial No. 125,122. In Switzerland February 25,

1936 4 Claims.

This invention relates to the manufacture of preparations for parenteral use having enhanced sexual hormone action by combining sexual hormones or their derivatives with a compound containing a carboxylic hydroxyl, an alcoholic hydroxyl or a carbonyl group, such as carboxylic acids, monoor dihydric alcohols, ketones or aldehydes. Both saturated compounds and compounds containing double or treble lin'kings have proved efiective.

The following table shows the effect of such activators on, for example, the action of the testosterone on young castrated rats (the weight of a rat at the time of castration was to grams; the experiment began 30 days after the castration). The animals received during 10 days daily each a subcutaneous injection of 50 'y of testosterone and the stated quantity of the compound named dissolved in 0.5 cc. of sesame oil. On the 11th day they were examined.

Weight in mg. Daily Compounds Formula dose in mg Seminal Prosvesicles tates w-hydroxy-tridecanoic acid. C1:H:t0a 10 132 124 whydror- -margaric acid-.. CHEMOL. 20 184 194 whydroxy-palmitic apid. Guano," 25 150 158 Pyruvic acid (3311403... 10 Q0 Pahnitic acid 0111111103.. 50 260 209 l2-hydroxy-steeric acid. ,CiaHuOaU Ricino'elnidic acid CnHi4O:.. 50 195 207 Stearic acid... CnHaaCa. 50 175 182 Behenolic acid C1zH|aO: 50 160 180 Camphor-Zi-carboxylic acid. CuHmOa-. 25 106 124 l2-ketostearic acid CnHnOz.. 25 125 50 160 186 Elaidic acid 013K140. 10 34 58 5 30 57 50 150 160 25 80 Brassidic acid. CnH4302-- 10 73 93 5 45 66 1 43 53 Bressidic acid without 50 14 38 CaHaOa- 1O 60 8O CnHx:O: 50 12B 178 CaHoOs--. 50 117 158 CiaHMOL- 50 111 129 u-crotonic acid 04111301. 50 90 124 50 85 109 Erucic acid CnHlaOL. 10 47 71 5 44 61 Oleic acid CnHu0a.. 50 60 73 Linoleic acld CuHu0: 50 53 B5 Ethyl alcohol-" C:HuO 50 82 98 Prcpyl alcohol'. 031130-..- 50 117 156 lsopropyl alcohol. CsHsO 50 120 150 Butyl alcohol. C4Hm 50 72 Hexyl alcohol, CoHu0 50 95 125 Octyl alcohol. CBHuO 50 77 Dodecyl alcohol. CnHa 50 95 98 Cetyl aloohol CisHn 50 165 Stearic slcohoL. nHnO... 50 200 220 Olelc alcohol CnHu 50 87 111 Cinnaniic alcohoL. CIHIO 50 80 81 Testosterone alone- 42 66 Sesame oil 14 41 Similar values were attained in combination with androstane diol, androstene-diol, andro stene-dione, methyl-testosterone or the like, as follows for example from the following table:

' With 50 mg. figgg gfi palmitic acid Daily weight in mg. g 'g Compounds dose Seminal Pros- Seminal Prosv tates v tates 17-methylt estosterone 50 58 88 160 210 l7-ethyld1hydrotestos- 500 49 108 70 148 terone 200 19 55 40 60 Androstane 3 cis 17 trans-dial. '200 74 239 308 Androstene-3-trans-l7- 1000 48 71 114 136 trans-diol. 500 30 50 99 120 Androstenedione 500 126 166 208 251 Values obtained with brassidic acid instead of palmitic acid.

Instead of sesame oil other oils or other solvents suitable for the parenteral introduction of medicaments or mixtures of such solvents may be used. Instead of the compounds listed above other substituted or unsubstituted carboxylic acids, monoor divalent alcohols, ethers, ketones or aldehydes, particularly those of the aliphatic series but also those of .a fatty aromatic nature, may be used alone or in combination with each other. Instead of the free acids their salts or esters with poly-alcohols or poly-oxy-ketones, these esters containing at least one free hydroxyl group, may be used, for instance the propane diol mono-palmitic acid ester, the glycerol monoor di-palmitic acid ester or the like. The substituted compounds may contain one or more subtives, for example oestrone, oestradiol and their esters as well as with progesterone.

Instead of the natural sexual hormones artificially made compounds of analogous'action may be similarly used. 1

The new preparations are useful in therapeutics as sexual hormone preparations.

What we claim is:

1. Preparations for parenteral use having enhanced sexual hormone action, obtained by combining a sexual hormone selected from the group consisting of testosterone, androstane-diol, androstene-diol, l7-methyl-testosterone, oestrone, oestradiol and androstene-dione with a compound selected from the group consisting of aliphatic carboxylic acids, aliphatic hydroxy-carboxylic acids and aliphatic alcohols.

2. Preparations for parenteral use having enhanced male sexual hormone action, obtained by combining testosterone with higher aliphatic Preparations for parenteral use having encarboxylic acids. hanced male sexual hormone action, obtained 3. Preparations for parenteral use having enby combining testosterone with higher aliphatic hanced male sexual hormone action, obtained alcohols.

5 by combining testosterone with higher aliphatic KARL MIESCHER.

hydroxy-carboxylic acids. ALBERT WE'ITS'I'EIN. 

